PDF(Pubmed)
Abstract：
Snakebite envenomation is a major public health issue which causes severe morbidity and mortality, affecting millions of people annually. Of a diverse range of clinical manifestations, local and systemic haemorrhage are of particular relevance, as this may result in ischemia, organ failure and even cardiovascular shock. Thus far, in vitro studies have failed to recapitulate the haemorrhagic effects observed in vivo. Here, we present an organ-on-a-chip approach to investigate the effects of four different snake venoms on a perfused microfluidic blood vessel model. We assess the effect of the venoms of four snake species on epithelial barrier function, cell viability, and contraction/delamination. Our findings reveal two different mechanisms by which the microvasculature is being affected, either by disruption of the endothelial cell membrane or by delamination of the endothelial cell monolayer from its matrix. The use of our blood vessel model may shed light on the key mechanisms by which tissue-damaging venoms exert their effects on the capillary vessels, which could be helpful for the development of effective treatments against snakebites.
摘要：
蛇咬伤毒害是一个主要的公共卫生问题，会导致严重的发病率和死亡率。每年影响数百万人。在各种临床表现中，局部和全身出血特别相关，因为这可能会导致缺血，器官衰竭甚至心血管休克。到目前为止,体外研究未能概括体内观察到的出血效应.这里,我们提出了一种器官芯片方法来研究四种不同的蛇毒对灌注微流体血管模型的影响。我们评估了四种蛇的毒液对上皮屏障功能的影响，细胞活力，和收缩/分层。我们的发现揭示了微脉管系统受到影响的两种不同机制，通过破坏内皮细胞膜或通过内皮细胞单层从其基质分层。使用我们的血管模型可以揭示组织损伤毒液对毛细血管产生影响的关键机制，这可能有助于开发针对蛇咬伤的有效治疗方法。
